The correlation between platelet responsiveness to clopidogrel and CYP2C19 polymorphism in patients with peripheral vascular disease

N.M. El-Khodary, A.M. El-Behery , N.A. El-Askary, H.M. Donia, G.A. Omran

Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt. nohamahmoud_55@hotmail.com

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• Pharmacogenomics

OBJECTIVE: Several patients undergoing endovascular intervention and bypass surgery present with high platelet reactivity following clopidogrel treatment. We aimed to determine the frequency of the genetic polymorphism of CYP2C19*2 and the contribution of this polymorphism along with other clinical parameters to clopidogrel response in an Egyptian population.

PATIENTS AND METHODS: A total of 50 patients receiving clopidogrel at a maintenance dose of 75 mg daily post vascular intervention from January 1, 2019, to May 30, 2020, were enrolled in this study. Clopidogrel resistance was determined through platelet aggregation analysis using Chrono-Log® platelet aggregometer. Single-nucleotide polymorphism (SNP) genotyping was performed using quantitative real-time polymerase chain reaction (QRT-PCR).

RESULTS: The incidence of clopidogrel resistance among this Egyptian population is about 22%. Univariate analysis demonstrated that CYP2C19*2 genotype (p = 0.001), high body mass index (BMI; p = 0.025), diabetes (p = 0.037),  high fasting blood glucose (FBG) level (p = 0.037), and high glycosylated hemoglobin (HbA1c) level (p = 0.004) were significantly associated with clopidogrel resistance. Multivariate analysis showed that CYP2C19*2 genotype (odds ratio (OR), 927.71; 95% confidence interval (CI), 1.915–449496.2; p = 0.030) and high BMI (OR, 1.789; 95% CI, 1.044–3.064; p = 0.034) were the most powerful predictors of clopidogrel resistance.

CONCLUSIONS: Clopidogrel resistance in patients with peripheral vascular disease is associated with the presence of CYP2C19*2 allele, obesity, and diabetes; these factors should be considered prior to clopidogrel administration

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